Development of the heart

The heart is one of the first organs in the developing embryo to form and function. By the start of week 4, a primitive heart has begun to pump blood and by week 7 most of the gross development of the heart is complete. Its development is complex, with several events occurring simultaneously.

This article aims to provide a brief overview of the key events:

• development of the heart fields

• heart folding and the development of the primitive chambers

• development of the heart septa

• development of the heart valves

• development of the outflow tracts

The development of the vascular system is not discussed in this article.

Early development (week 3)

The development of the heart begins from day 15-16 with gastrulation. Progenitor heart cells from the epiblast migrate into the primitive streak and form the heart field, a horseshoe-shaped part of the lateral splanchnic mesoderm cranial to the neural folds. Across several days, this mesoderm differentiates into myoblasts that form two endocardial tubes and their accompanying pericardium, on either side of the fetus ¹. Cellular signalling that will establish laterality of the body is also occurring throughout this early period and defects in this can cause dextrocardia, situs inversus and other cardiac defects ².

Folding of the body occurs concurrently around this time. By day 22, folding has merged the two endocardial tubes into a singular, beating primordial heart tube. The heart tube, located in the thorax, is suspended by a dorsal mesocardium in the pericardial cavity. Eventually, the dorsal mesocardium regresses, leaving the heart suspended in the pericardium by its vessels. The transverse pericardial sinus represents the remnant of the dorsal mesocardium ².

Although this distinction is not meaningful until looping has begun or completed, for simplicity, the heart tube can be divided into five structures (from cranially to caudally):

1. truncus arteriosus

2. bulbus cordis

3. primitive ventricle

4. atrium

5. sinus venosus

From day 23 the parts of the heart tube begin to bulge and undergo looping, initially forming a C-shaped loop then finally an S-shaped loop. By day 28 this looping is complete, now with the bulbus cordis on the right, the ventricle on the left and both flanked dorsally by the atrium and sinus venosus ^2,3. 

Heart tube looping results in fusion and internal communication of its different parts. An atrioventricular (AV) canal now connects the atrium and ventricle. The bulbus cordis and the primitive ventricle communicate through the primary interventricular foramen. Trabeculation occurs in both the primitive ventricle and the bulbus cordis distal to the interventricular foramen forming the left and right primitive ventricles, respectively.

Further development of the heart chambers (weeks 4-6)

The processes described below occur somewhat simultaneously across approximately two weeks. For simplicity, this process is divided by anatomical location.

Atrial growth

Two concurrent events contribute to atrial development, occurring through the 4^th week:

1. sinus venosus growth

   • in early development the sinus venosus has two horns, a left and a right horn

   • initially, both horns begin receiving blood from the vitelline vein, umbilical vein and common cardinal vein

     • however, changes associated with venous system development causes the left sinus horn to regress over time, leaving a prominent right sinus horn

   • the left sinus horn ultimately becomes the coronary sinus and oblique vein of the left atrium

   • the right sinus horn becomes the sinus venarum (smooth right atrium) receiving the superior and inferior vena cava

2. primitive atrial growth

   • the remnants of the embryonic atrium will become the trabeculated atrial appendages

   • externally the left atrium expands and develops a single outgrowth - the pulmonary vein

   • the pulmonary vein attaches to the veins of the lung buds and will divide into multiple pulmonary veins

     • As the left atrium grows, these veins will ultimately be incorporated into it as the smooth left atrium

   • trabeculated right atrium fuses with the sinus venarum ^{2, 3}

Atrial septation

• by the end of week 4, the septum primum has begun developing, growing from the roof of the common atrium

• concurrently, atrioventricular endocardial cushions develop within the heart.

• septum primum grows down towards these cushions – the space between these structures is the ostium primum and allows inter-atrial communication

• before complete fusion of the septum primum to the AV cushions, apoptosis forms an ostium secundum at the top of the septum primum

• growth of the atria facilitates the formation of another partition, the septum secundum. This similarly grows from the atrial roof but does not completely divide the two cavities - the space it leaves is the foramen ovale.

• apoptosis of the septum primum continues and it loses its attachment to the roof of the atrium – thus it becomes the valve of the foramen ovale and this will persist until birth ²

Atrioventricular canals

• 4 atrioventricular endocardial cushions exist: two lateral, an anterior and a posterior – these encircle the atrioventricular canal

• during week 5 the anterior and posterior cushions project into the canal and divide the canal into a left and right atrioventricular orifice

• after fusion of the atrioventricular endocardial cushions, a thin layer of mesenchymal tissue begins to proliferate about the atrioventricular orifice

  • the surrounding ventricular myocardium disappears (either through erosion from blood flow or apoptosis) such that these mesenchymal proliferations are attached to the ventricles via thin muscular tissue.

    • these proliferations become the AV valves

    • the thin muscular tissue reorganises into chordae tendineae and remains attached to the heart wall via papillary muscles ^{2, 4}

Great vessel formation

• during week 5 endocardial cushions also appear in the truncus arteriosus – these form the truncal septum

  • this septum spirals as it grows away from the heart, dividing the truncus into the pulmonary and aortic channels

• endocardial cushions also develop in the walls of the conus cordis and form a conal septum that divides the conus into an anterolateral and posteromedial portion – these will become the smooth-walled right and left ventricular outflow tracts respectively

• conotruncal septum forms by union of the two septa described above. Defects in its formation unsurprisingly cause great vessel malformation e.g. transposition of the Great Vessels, tetralogy of Fallot

Ventricular septum formation

• begins at the end of week 4

• the two primitive ventricles expand with their medial walls merging to form the muscular interventricular septum, which does not completely separate the two ventricles (i.e. a physiological interventricular foramen exists)

• the conotruncal septum descends and fuses with the muscular interventricular septum, closing the interventricular foramen and forming the membranous part of the interventricular septum

• the semilunar valves separately form as outpouchings of the truncal endocardial cushions ³

Summary

Once complete, the following structures have developed from several embryological precursors:

• left atrium

  • primitive atrium (trabeculated left appendage)

  • pulmonary vein incorporation (smooth part)

• right atrium

  • primitive atrium (trabeculated part)

  • sinus venosus (smooth part)

• left ventricle

  • primitive ventricle (trabeculated part)

  • conus cordis (outflow)

• right ventricle

  • bulbus cordis (trabeculated part)

  • conus cordis (outflow)

• AV valves (AV endocardial cushions)

• semilunar valves (truncal endocardial cushions)

• great vessels

  • truncus arteriosus

  • truncal endocardial cushions